[1]张 莹),李青菊),李江雁),等.氧化苦参碱对糖尿病大鼠骨代谢及CREB/CRTC1信号通路的影响[J].郑州大学学报(医学版),2021,(01):112-118.
 ZHANG Ying),LI Qingju),LI Jiangyan),et al.Effects of oxymatrine on bone metabolism and CREB/CRTC1 signaling pathway in diabetic rats[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2021,(01):112-118.
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氧化苦参碱对糖尿病大鼠骨代谢及CREB/CRTC1信号通路的影响()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2021年01期
页码:
112-118
栏目:
应用研究
出版日期:
2021-01-20

文章信息/Info

Title:
Effects of oxymatrine on bone metabolism and CREB/CRTC1 signaling pathway in diabetic rats
作者:
张 莹1)李青菊2)李江雁1)吴苏豫1)周艳红1)
1)新乡市中心医院内分泌科 河南新乡 453000 2)郑州大学第二附属医院内分泌科 郑州 450014
Author(s):
ZHANG Ying1) LI Qingju2) LI Jiangyan1) WU Suyu1) ZHOU Yanhong1)
1)Department of Endocrinology, Xinxiang Central Hospital, Xinxiang, Henan 4530002)Department of Endocrinology, the Second Affiliated Hospital,Zhengzhou University,Zhengzhou 450014
关键词:
糖尿病 氧化苦参碱 骨代谢 骨密度 CREB/CRTC1信号通路
Keywords:
diabetes oxymatrine bone metabolism bone density CREB/CRTC1 signal pathway
分类号:
R587.1
摘要:
目的:探讨氧化苦参碱(OMT)对糖尿病大鼠骨代谢相关指标与CREB/CRTC1信号通路的影响。方法:40只SD大鼠分为正常对照组、糖尿病模型组、OMT低剂量组、OMT高剂量组,每组10只。糖尿病模型组和OMT低、高剂量组大鼠腹腔注射链脲佐菌素(STZ)构建糖尿病模型,OMT低、高剂量组大鼠在建模结束后分别给予100、200 mg/kg OMT灌胃,每日1次且持续7 d。给药结束24 h后邻甲酚酞络合铜比色法检测尿钙和血清钙、磷含量,ELISA法测定血清Ⅰ型胶原C端肽(CTX-Ⅰ)、骨钙素(OC)及骨特异性碱性磷酸酶(BSAP)的含量。4周后取大鼠股骨,双能X射线检测骨密度,qRT-PCR检测股骨组织中ALP、CEBP、OPG、RANKL mRNA的表达水平,HE染色观察骨组织病理形态学改变,免疫组化染色检测股骨组织中OCN蛋白的表达,Western blot检测股骨组织中p-CREB、t-CREB、CRTC1蛋白的表达。结果:与正常对照组比较,糖尿病模型组和OMT低、高剂量组大鼠24 h 尿量与尿钙含量升高,血清中CTX-Ⅰ、OC、BSAP的含量增加,骨密度降低,ALP、OPG mRNA表达下调,CEBP、RANKL mRNA表达上调; 股骨组织中骨小梁减少、排列稀疏、断裂,OCN蛋白表达降低,p-CREB和CRTC1的蛋白表达上调,差异均有统计学意义(P<0.05)。与糖尿病模型组比较,OMT低、高剂量组血清中CTX-Ⅰ、OC、BSAP的含量降低,骨密度增加,ALP mRNA表达上调,CEBP、RANKL mRNA表达下调; 股骨组织中骨小梁有所增加、排列与连续性较好,OCN蛋白表达升高; OMT高剂量组p-CREB和CRTC1的蛋白表达下调,差异均有统计学意义(P<0.05)。与OMT低剂量组比较,OMT高剂量组OPG mRNA表达上调,差异有统计学意义(P<0.05)。结论:氧化苦参碱可以促进糖尿病大鼠骨形成,并有效抑制骨吸收,其作用可能与抑制CREB/CRTC1信号活化有关。
Abstract:
Aim:To investigate the effects of oxymatrine(OMT)on bone metabolism and CREB/CRTC1 signaling pathway in diabetic rats.Methods:A total of 40 SD rats were randomly allocated into normal control group, diabetic group, OMT low dose group, OMT high dose group,and each group had 10 rats.Intraperitoneal injection of streptozotocin(STZ)in latter 3 groups were performed to induce diabetes model.The rats in the OMT low and high dose groups were given intragastric administration of 100 and 200 mg/kg OMT, respectively, once a day for 7 days.24 hours after the end of the administration, O-cresolphthalein complex copper colorimetric assay was used to determine urine calcium,and serum calcium and phosphorus,and ELISA was used to determine the serum type Ⅰ collagen C-terminal peptide(CTX-Ⅰ), osteocalcin(OC)and bone specific alkaline phosphatase(BSAP).After 4 weeks, the femur of the rat was taken.Dual energy X-ray was adopted to detect bone density.qRT-PCR, to detect the mRNA expression levels of ALP, CEBP, OPG, RANKL in femoral tissue,HE staining,to observe the pathological and morphological changes of bone tissue, immunohistochemical staining, to detect the expression of OCN protein in femoral tissue, Western blot, to detect the expressions of p-CREB, t-CREB, CRTC1 protein in femoral tissue.Results:Compared with the normal control group, the 24-hour urine volume and 24-hour urine calcium content of the diabetes model group, the OMT low and high dose groups increased, the contents of CTX-Ⅰ, OC, BSAP in serum increased, bone density decreased, ALP and OPG mRNA expression levels were down-regulated,CEBP and RANKL mRNA expression levels were up-regulated(P<0.05), rats had varying degrees of trabecular bone loss, sparse arrangement, and fracture.OCN protein expression in the femur reduced, the protein expression levels of p-CREB and CRTC1 were up-regulated(P<0.05).Compared with the diabetic model group, the levels of CTX -Ⅰ, OC and BSAP in serum of OMT low and high dose groups decreased, bone mineral density and ALP mRNA expression level increased,CEBP and RANKL mRNA expression levels decreased, trabecular bone increased, arranged and continuous well, and the expression of OCN protein increased,p-CREB and CRTC1 protein expression was down-regulated in the OMT high dose group. Compared with the OMT low dose group, OPG mRNA expression was up-regulated in the OMT high dose group(P<0.05).Conclusion:OMT can promote bone formation in diabetic rats and effectively inhibit bone resorption, which may be related to the inhibition of CREB/CRTC1 signal activation.

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备注/Memo

备注/Memo:
【基金项目】河南省重点科技攻关计划项目(182104310026)
【作者简介】张莹,通信作者,女,1986年4月生,硕士,主治医师,研究方向:糖尿病骨代谢的发病机制,E-mail:zhangying_200886@126.com
更新日期/Last Update: 2021-02-15